Confusion
Confusion is a state in which the patient cannot take into account all elements of his/her immediate environment, implying an element of sensorial clouding. Apathy and drowsiness are often prominent and accompanied by disorientation primarily for time, less often for place, and rarely for self. Motor abnormalities such as tremor, asterixis and difficulty in motor relaxation may occur.
Mild confusional states are common, especially in elderly patients exposed to hospital care or the trauma of major surgery. Metabolic encephalopathy due to systemic organ failure especially of the liver or kidneys, excessive medication, nutritional insufficiency or systemic infection with fever often add to an underlying traumatic, vasometer or senile cerebral insufficiency precipitating a confusional state. A severely confused person is usually unable to carry out more than a few simple commands. Speech may be limited to a few words or phrases or occasionally the patient may be quite talkative. The confused patient will react to both verbal and painful stimuli although the response may be sluggish and slower than normal.
Delirium
Delirium is a common and difficult problem especially in ill elderly patients. It is characterized by a fluctuating disturbance in consciousness and change in cognition that usually develops over a short period of time. Ten to fifteen percent of elderly patients may be delirious on arrival to the hospital and up to 55% may become delirious following admission. Delirium is often accompanied by increased morbidity and subsequent functional decline. The financial consequences are also significant because of increased hospitalization and additional care requirements.
The signs and symptoms of delirium include disorientation which is sometimes total and inclusive of absence of self-recognition. Other characteristic findings are irritability, perceptual delusions, visual hallucinations and usually intermittent impairment of arousal, but there may be sustained insomnia. The symptoms of delusion usually become worse after nightfall. Many delusional patients are febrile, most are tremulous and those with drug or alcohol withdrawal may convulse. The severe agitation, disorientation and occasional presence of auditory rather than visual hallucinations sometimes can be confused with a functional psychosis, but in most cases, the presence of fever, defects in orientation, the impairment of simple calculations and intellectual tools identify the organic nature of the underlying mechanism. The delusional patient will respond to both verbal and painful stimuli.
Delirium most often occurs with widespread toxic or structural brain disease. It is seen especially during withdrawal from intoxication in abusers of drugs and alcohol and in acute inflammatory disorders such as meningitis and encephalitis. However, recent research suggest that specific disruptions of neurologic pathways and neurotransmitter systems may lead to delirium rather than “global†cerebral involvement.
Obtundation
Obtundation is primarily characterized by reduced alertness and hypersomnia. Hypersomnia is technically defined as a state of sleep in excess of 25% of the expected normal. When awakened from an obtunded state, the patient remains drowsy and confused and wakefulness can only be maintained by continuous verbal and painful stimuli. It is common to see the patient spontaneously changing postures in bed, drawing up the bed-sheets, and trying to pull out intravenous needles and indwelling catheters. The patient can accurately locate the source of painful stimulus and fights forcibly, sometimes accompanying the response with vocalization and grimacing. Asymmetry of spontaneous movement or of the response to a painful stimulus by an obtunded patient may indicate the association of obtundation with a hemiparesis or monoparesis.
Obtundation is often seen with substance abuse in the form of narcotic or alcohol overdosage. It is also seen in diffuse encephalopathic processes such as hepatic encephalopathy, diabetic acidosis and uremia. In obtundation secondary to substance abuse or diffuse encephalopathy, prompt diagnosis and appropriate therapy is urgent since the usual progression is to coma and possible death.
Primary causes of obtundation are rare, the prime example being the cerebral phase of African trypanosomiasis, a disease confined to tropical Africa. Obtundation may be seen in the various vector-borne types of encephalitis such as caused by the arboviruses including the equine encephalitides, Nile River encephalitis and herpes encephalitis. Occasionally, obtundation will accompany the various childhood†diseases such as mumps, varicella and measles. Fortunately, the disease known as encephalitis lethargica, a cause of obtundation seen between 1920 and 1940, and a common precursor of post-encephalitic parkinsonism, is no longer seen.
In the absence of indications that an underlying infectious or metabolic mechanism may be responsible, protracted obtundation may be related to localized disease such as space-occupying lesion adjacent to the hypothalmus and midbrain. Occasionally, obtundation will occur as a neurologic complication of systemic cancer.
Stupor
Stupor is unresponsiveness from which the patient can only be aroused by vigorous repeated painful stimuli. There is no response to verbal stimuli, and the response to pain becomes progressively less as the level of stupor deepens. The patient is unable to localize the site of the painful stimuli and, at best, the response is slow and stereotyped. Mental and physical activity is reduced to a minimum. Although unresponsive to many stimuli, the patient can open his/her eyes, look at the examiner and does not appear to be unconscious. Deep tendon reflexes are usually intact, but there may be evidence of muscle twitching, restless or stereotyped motor activity and grasping and sucking reflexes.
Catatonic stupor is seen most commonly in young people affected by catatonic schizophrenia. The patient lies with eyes open or tightly closed, resisting passive eye opening. There is an absence of spontaneous movements.
Coma
The patient who appears to be asleep and is at the same time incapable of responding adequately to either external stimuli or internal needs is in a state of coma. Coma may vary in degree from light to medium to deep. At its deepest stages, no reaction of any type is obtainable from the patient. Corneal, pupillary, pharyngeal, tendon and plantar reflexes are all absent. Opisthotonos and extensor rigidity of the limbs are suggestive of a decerebrate state. Respirations are often slow and Cheynes-Stokes in character. In lighter stages of coma (sometimes referred to as semicoma), most of the above mentioned reflexes can be elicited. Very painful stimuli may cause the patient to stir or moan.
The Glasgow Coma Scale (GCS) is the most widely accepted method for the evaluation and classification of coma, especially for head-injured patients. As shown in Table 2, the GCS grades three neurologic parameters. Patients who open their eyes spontaneously, obey commands and are oriented score a total of 15 points, the best possible score, whereas flaccid patients, who neither open their eyes or verbalize, score the minimum of 3 points. A GCS score of 8 or less is the generally accepted definition of coma. Those with a GCS of 8 or less are classified as severe, while those with a GCS score of 9 to 12 are categorized as moderate and those with a GCS score of 13 to 15 are mild.
Coma grades 3 to 5 indicate potentially fatal damage, especially if accompanied by fixed pupils or absent oculovestibular responses. Conversely, scores of 9 and above correlate with good recovery.
Demographics / Epidemiology
An altered state of consciousness may occur at any age from infancy to old age, in either sex, and without regard to ethnicity. Certain mechanisms for the production of ALC do occur preferentially in certain susceptible groups. For example, traumatic brain injury (TBI) is the leading cause of death and disability under the age of 45 in the United States with motor vehicle accidents being responsible for most head injuries. Each year in the United States, approximately two million people receive medical care for head injuries, 75,000 people die from head injury and 100,000 head-injured individuals are permanently disabled. The national cost of head injury is more than $39 billion a year.
Metabolic encephalopathies are the most common causes of ALC and in many large general hospitals, account for more than one half of patients with coma of undetermined etiology. Metabolic encephalopathies, such as are seen in kidney and hepatic failure, occur more frequently in middle and older age groups whose underlying disorder have had time to progress to the point of organ failure. The same is true for hypertensive encephalopathy. Altered states of consciousness due to alcohol excess are seen more commonly in men, but other substance abuse, such as with cocaine and opiates, is seen without gender preference, and unfortunately the incidence in adolescents and young adults has risen dramatically in the past four decades.
Diagnosis
It is imperative that immediate therapeutic measures take precedence over diagnostic or other procedures, and before embarking on efforts to establish an etiological basis for an altered state of consciousness of unknown origin. The physician must take urgent and immediate steps to correct factors that, if neglected, could produce irreversible damage or death. It should be established that the patient has a clear and unobstructed airway. Vital signs should be checked to determine the presence of shock or hypothermia. If there is a suspicion that hypoglycemia and/or substance abuse might be factors, 50% glucose and/or naloxone may be administered intravenously after a blood sample for chemical analysis has been drawn. Only after these potentially life-saving measures have been taken can the physician proceed with the history and complete examination.
History In the absence of a history from family, friends or witnesses, it is important to bear in mind that the individual may carry on his/her person information regarding medical illnesses in the form of cards, medallions, medical alert systems, etc. The police can be of great help in finding relatives or associates. The person or persons accompanying the patient should not be permitted to leave until they have been questioned. When present, observers and relatives should be questioned about the mode of onset or the occurrence of an injury; the use of drugs, alcohol or other toxic substances; infections; convulsions; headache and previous illnesses (e.g., diabetes melitus, nephritis, heart disease, hypertension). Containers suspected of having held food, alcohol, drugs or poisons should be examined and saved for chemical analysis and possible legal evidence. The patient’s age is a significant component of the medical history. Epilepsy and systemic infections are most common under the age of 40, whereas cardiovascular disease, especially stroke, metabolic disorders and uremia are most common after the age of 40.
Tramatic Brain Injury
Evidence of head trauma should be sought by carefully palpating the scalp and looking for an accumulation of blood in the subcutaneous orbital and mastoid regions and behind the tympanic membrane. In patients with head trauma, there may be an associated fracture of cervical vertebrae and appropriate precautions should be taken to avoid injury to the spinal cord. It is not unusual for a patient with a head injury to be initially stable and awake and to deteriorate rapidly. This is typical of a hematoma or an expanding contusion that is amenable to surgery. In all patients with a history of trauma, bleeding sites should be identified and the patient handled with care to avoid compounding simple fractures.
The General Physical Exam Vital Signs
The vital sign determinations may contribute important clues to the underlying process responsible for the altered level of consciousness. Fever suggests the presence of a sever systemic infection such as pneumonia, bacterial meningitis, or a brain lesion that has disturbed the temperature-regulating centers. An excessively high body temperature, _____ ______, associated with dry skin should raise suspicion of heat stroke. Hypothermia is frequently observed in alcoholic or barbituate intoxication, extracellular fluid deficit, or in shock and peripheral circulatory failure. Slow respirations suggests barbituate, morphine, or other narcotic intoxication, whereas rapid deep breathing (Kussmaul respirations) suggests diabetic or uremic acidosis but may also occur in intracranial disease. Rapid breathing accompanied by an expiratory grunt and associated with fever is a common finding in lobar pneumonia. Diseases that elevate the intracranial pressure or cause damage to the brain, especially the brain stem, often cause slow, irregular or periodic (Cheynes-Stokes) breathing. Exhalation through pursed lips is suggestive of hypokalemia. Apneustic breathing is characterized by a pause of 2-3 seconds between inspiration and expiration and is attributed to a lesion in the pontine respiratory center. Ataxic respirations are manifested by an irregular pattern of inspiratory and expiratory respirations seen in association with lesions in the medullary respiratory center. If the pulse is exceptionally slow, it suggests a heart block and the possibility of Stokes-Adams syndrome, or if combined with hypertension and periodic breathing, increased intracranial pressure. A tachycardia of 150 or above suggests an arrhythmia with possible insufficiency of cerebral circulation. The presence of atrial fibrillation suggests the possibility of a cerebral embolism. Blood pressure observations are important. Marked hypertension occurs with cerebral hemorrhage and hypertensive encephalopathy and at times with increased intracranial pressure. Hypotension is seen in diabetic coma, alcohol or sedative drug intoxication or in loss of blood due to internal hemorrhage.
The Ocular Fundi
Careful observation of the optic fundi without the use of mydriatics that interfere with pupillary reflexes may produce information about hypertension, systemic arteriosclerosis, diabetes mellitus, hemorrhages, and the presence or absence of papilledema. If a lesion is suspected that is producing elevated intracranial pressure, examination of the ocular fundi for the presence or absence of papilledema should be considered an emergency procedure. Examination of the Skin Inspection of the skin may also yield valuable clinical information. Multiple bruises, especially in the scalp area, suggest cranial trauma. Bleeding from the nose, an ear or orbital hemorrhage also raises the possibility of trauma. Marked pallor suggests internal hemorrhage. Rashes are seen in a number of infectious diseases including meningococcemia, endocarditis, typhus, or Rocky Mountain fever. The dementia of pellagra is usually accompanied by typical skin lesions on the face and hands and diarrhea. The physician should examine the skin closely for evidence of needle marks suggestive of substance abuse or insulin usage.
Odor of the Breath
Often neglected, the odor of the breath may afford a valuable diagnostic clue. The odor of alcohol is easily recognizable, but may be a misleading clue that detracts from a more significant diagnosis. The “fruity†odor of diabetic acidosis, the uriniferous odor of uremia, and the musty, “mousy†odor of hepatic coma are sufficiently distinctive to provide valuable diagnostic clues. While checking breath odor, the physician has the opportunity to inspect the mouth for evidence of tongue-biting and gum hypertrophy, tell-tale evidence of epilepsy and anti-convulsant drug use.
Cardiorespiratory and Abdominal Examinations
The heart should be examined for the apical pulse rate and rhythm, the presence of murmurs and cardiac enlargement, as well as for evidence of congestive heart failure and carotid artery bruits and hemodynamics. The extremities should be examined for peripheral pulses, evidence of sclerosis, cyanosis, edema and clubbing of the fingers. The character of breathing should be noted and the lungs examined for evidence of percussive and auscultatory evidence of infiltration, consolidation, fluid or congestion. The abdominal examination should include evidence of hepatomegaly and the presence of masses. A rectal examination should include evaluation of the prostate and examination of the stool for occult or gross blood.
The Neurological Examination Observation of the Patient
Careful observation of the obtunded, stuporous or comatose patient may yield considerable information concerning the function or lack of function of various parts of the nervous system. One of the most helpful procedures is to sit at the patient’s bedside for five to ten minutes and observe what he/she does. The predominant postures of the body, the position of the head and eyes, the rate, depth and rhythm of respiration, and the pulse should be noted. The state of responsiveness should then be estimated by noting the patient’s reaction to verbal commands, his/her capacity to execute a simple response and the response to painful stimuli. The obtunded patient is usually capable of accurately localizing a painful stimulus and will fight forcefully against it accompanied by grimacing and vocalization. As unconsciousness progresses toward coma, these reactions may be replaced by stereotyped responses having specific anatomic or pathologic connotations. These “posturing†responses include the following: Decorticate posture or rigidity includes flexion of the arms and wrists with the legs extended with internal rotation and plantar flexion. This posture suggests severe bilateral damage in the hemispheres above the midbrain with involvement of the corticospinal tracts. Decerebrate posture or rigidity includes pronation and extension of the arms and extension of the legs with plantar flexion occasionally accompanied by opisthotonos and trismus. This posture suggests damage to the corticospinal tracts arising in the midbrain or caudal diencephalon. Abnormal posturing or motor activity is also seen under other circumstances. External rotation of a leg or lack of restless movements on one side suggest a hemiparesis. Multifocal myoclonus, characterized by sudden, generalized muscle contractions, are commonly seen in metabolic disorders especially uremia, anoxia or drug ingestion. Asterixis (palmar flipping) is commonly seen in metabolic encephalopathies associated with drowsiness and confusion. It is most commonly seen in hepatic encephalopathy and has been attributed to accompanying ammonia intoxication.
Pupillary and Brainstem Reflexes
Pupillary reflexes depend on the correct functioning of centers situated in the brainstem (diencephalon, pons and midbrain) and provide valuable information on the localization of lesions in the brainstem. Symmetrically reactive round pupils, 2.5 to 5 mm in diameter, usually exclude midbrain damage as a cause of coma. One enlarged (greater than 5 mm in diameter) unreactive or poorly reactive pupil usually results from either an intrinsic midbrain lesion on the same side or, far more commonly, is secondary to stretching or compression of the third nerve (oculomotor) by the secondary effects of a mass. Oval and slightly eccentric pupils accompany early midbrain-third nerve compression. Bilaterally dilated and unreactive pupils indicate severe midbrain damage usually by compression from transtentorial herniation or from anticholinergic drugs. Small, but not pinpoint, pupils (1 to 2.4 mm in diameter) that react are most commonly seen in metabolic encephalopathies. Bilateral pinpoint pupils that still react (but may require a magnifying glass to verify) are characteristic of narcotic or barbiturate overdose but may also occur as the result of a pontine hemorrhage. Skew deviation of the eyes (one up or down) is an indication of a brainstem lesion. Forced downward deviation of the eyes such as looking at one’s nose has been described in cases of thalamic hemorrhage and is usually accompanied by pinpoint nonreactive pupils.
Eye Movements
Eye movements are an additional valuable component of the neurological examination, contributing information concerning the location of the etiological mechanism causing an altered level of consciousness. The eyes are first observed by elevating the lids and noting the resting position and spontaneous movements of the globes. Unconscious patients, in whom the centers that mediate eye movements are intact, commonly have a slightly divergent straightforward gaze and slow, horizontal conjugate eye movements (roving eye movements). In these patients, turning the head briskly from side to side elicits conjugate eye movements directed opposite to the head rotation. This is the oculocephalic or doll’s head reflex which is absent in the normal alert individual. Cyclic vertical downward movements are seen in specific circumstances. “Ocular bobbing†describes a brisk downward and slow upward movement of the globes associated with loss of horizontal eye movements and is diagnostic of bilateral pontine damage. “Ocular dipping†is a slower arrhythmic downward movement followed by a faster upward movement in patients with normal reflex horizontal gaze and denotes diffuse anoxic damage of the cerebral cortex. The oculovestibular response is elicited by caloric stimulation of the semicircular canals by irrigating the external ear canal with cold water. This produces tonic bilateral eye deviation toward the stimulated side. In a normal awake individual, this type of stimulation causes nystagmus away from the stimulated side. Full horizontal excursion of the eyes to both sides is possible only when the nuclei and the internuclear connections between the third and sixth nerves are intact. A normal oculovestibular response indicates that the cause of unconsciousness is not a structural brainstem lesion. Unilateral lesions in the pontine gaze center adjacent to the sixth nerve nucleus result in a paralysis of ipsilateral gaze and contralateral deviation of the eyes and a failure of caloric stimulation to move the eyes beyond the midline. Conjugate horizontal ocular deviation at rest or incomplete conjugate eye movements with head turning indicate damage in the pons on the side of the gaze paresis or frontal lobe damage on the opposite side. This phenomenon may be summarized by the following aphorism: The eyes look toward a hemispheral lesion and away from a brainstem lesion. The pathway that connects the pontine gaze center to the midbrain oculomotor nuclei is called the medial longitudinal fasciculus (MLF). When its fibers are damaged, the ipsilateral medial rectus muscle fails to contract when required for voluntary or reflex conjugate horizontal gaze. This is called internuclear ophthalmoplegia and can be demonstrated in the unconscious patient by either oculocephalic or oculovestibular testing.
Testing Office and Laboratory
Blood chemistry tests are made routinely to investigate metabolic, toxic or drug-induced encephalopathies. The major areas of metabolic abnormalities encountered in clinical practice are those of electrolytes (sodium, potassium, chloride), calcium, blood urea nitrogen (BUN), serunm creatinine (Cr), glucose and hepatic dysfunction (ammonia). Toxicological analyses are of great value in any case of ALC where the diagnosis is not immediately apparent. However, the presence of exogenous drugs or toxins, especially alcohol, does not ensure that other factors, particularly head trauma, may not also contribute to the clinical state. The legal blood level above which alcohol is incriminated as a possible etiologic factor is 100 mg/dl in most states. Ethanol levels of 200 mg/dl in individuals who are non-habituated to alcohol generally cause confusion, and levels above 300 mg/dl are associated with stupor. The development of tolerance may allow the chronic alcoholic to maintain wakefulness above these levels.
Radiologic Studies
Skull roentgenograms, especially in cases of craniofacial trauma, are essential in detecting fractures, shifts of the pineal body from the midline, and abnormal calcifications. In the case of trauma and the possibility of vertebral damage, roentgenograms of the cervical and thoracic spine must be taken. Computerized tomography (CT) scanning and magnetic resonance imaging (MRI) yield information about structural damage in the supratentorial area and are well-suited for visualizing and diagnosing hemorrhages, tumors, hydrocephalus and brain edema and/or softening due to cerebral thrombosis or emboli. Patients for CT or MRI studies should be carefully selected because most cases of ALC are metabolic or toxic in origin. The notion that a normal CT scan excludes an anatomic lesion, however, is erroneous. Early bilateral hemisphere infarction, small brainstem lesions, encephalitis, meningitis, decreased or absent cerebral perfusion, superior saggital sinus thrombosis and even subdural hematomas that are isodense to adjacent brain may be overlooked. Even MRI may fail to demonstrate these processes early in their evolution. Nevertheless, in coma of unknown etiology, a CT or MRI scan should be obtained. In mass lesions, shifting of the pineal body correlates roughly with the level of consciousness. Three to 5 mm of horizontal displacement of the pineal body from the midline correlates with obtundation; 5 to 8 mm correlates with stupor; and greater than 8 mm displacement correlates with coma.
The Electroencephalogram (EEG)
The EEG tests neuronal physiology and therefore is important in the diagnosis and follow-up of metabolic or drug-induced encephalopathies. It is seldom diagnostic in cases of coma except to identify clinically unrecognized seizures. Specific EEG patterns have been described in metabolic coma due to hepatic failure and other mechanisms. A pattern described as “alpha coma†has been associated with either high pontine or diffuse cortical damage and is indicative of a poor prognosis.
Cerebrospinal Fluid (CSF) Examination
CSF examination is important when the differential diagnosis includes the possibility of meningitis, encephalitis or subarachnoid hemorrhage in which the CT is normal. In general, the CT has replaced the lumbar puncture as a diagnostic test in intracerebral hemorrhage. Spinal fluid pressure, cell count and differential, levels of protein and sugar, culture and viral studies are useful diagnostic contributions made by examination of the CSF. Differential Diagnosis In many instances, an altered state of consciousness spanning the spectrum of confusion through coma is part of an obvious medical problem such as known drug ingestion, hypoxia, stroke, trauma, or liver or kidney failure. Attention is then appropriately focused on the primary underlying illness. Some general rules are helpful in establishing the diagnosis if the underlying cause is unknown. Coma that appears subacutely or slowly is usually related to preceding medical or neurologic problems, including the secondary edema that surrounds a pre-existing lesion. Illnesses that cause sudden or acute coma are due to drug ingestion or to one of the catastrophic brain lesions such as hemorrhage, trauma, hypoxia or rarely, acute basilar artery thrombosis.
The demonstration of focal brain disease or meningeal irritation with CSF abnormality and abnormalities in the CT, MRI or EEG, helps in the differential diagnosis of ALC. For purposes of differential diagnosis, the diseases that frequently result in ALC can be conveniently divided into three classes as shown in Table 3.